tbuckley/cabot-search huggingface dataset:
Depth of metabolic response at interim PET and survival outcomes among patients with primary refractory and early relapsing diffuse large B-cell lymphoma (DLBCL).
Authors: Allison Marie Bock, Raphael Mwangi, Fatemah Ataei, Matthew Thorpe, Matthew J. Maurer, Joshua Pritchett, Jacob Tyler Shreve, Jonas Paludo, Arushi Khurana, James Robert Cerhan, Thomas E. Witzig, Thomas Matthew Habermann, Yucai Wang, Jason R. Young, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2023)

7543 Background: Total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) may improve upon standard 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)-based assessment of advanced DLBCL during treatment. We report the association of TMTV and SUVmax changes at interim PET-CT (PET2) on survival outcomes in patients with primary refractory DLBCL (prDLBCL) and early relapsing DLBCL (erDLBCL). Methods: Adult patients with prDLBCL (less than a complete response (CR) or progression by the end of treatment (EOT)) or erDLBCL (CR at EOT with relapse within 12 months) between 2005 and 2019 at Mayo Clinic Rochester were included. The % change (Δ) from baseline to PET2 (after 2 cycles of 1L therapy) of TMTV and SUVmax were measured. A PET segmentation threshold of 1.5 liver mean SUV + two standard deviations with a minimum volume constraint of 0.5 mL was utilized (MIM Software, Inc., Cleveland OH, USA) with manual input as needed. Functional splines analysis determined SUVmax and TMTV threshold for analysis. Results: 131 patients had complete PET-CT data (N=79 prDLBCL, N=52 erDLBCL). Baseline median TMTV and SUVmax were 767.4 cm 3 (range 0.9-6840.4) and 20.5 (2.0-52.6), respectively. At a median follow up of 77.6 months, 81 patients had died. 2-year OS rate was 53% (95% CI: 42-67) for patients with a PET2 ΔSUVmax decline ≥65% compared to 15% (95% CI: 7-29) for patients with a PET2 ΔSUVmax decline &lt;65%(p&lt;0.001). PrDLBCL had a 2-year OS rate of 48% (95% CI: 31-74) for a ΔSUVmax ≥65% compared to 7% (95% CI: 2-21) for a ΔSUVmax &lt;65%(p&lt;0.001), which captured 58% of prDLBCL patients (N=46). Two-year OS rate was 43% (95% CI: 34-54) for patients with a ΔTMTV ≥75% compared to 5% (95% CI: 1-35) for patients with ΔTMTV &lt;75% (p&lt;0.001). All patients with a ΔTMTV &lt;75% had prDLBCL. PrDLBCL had a 2-year OS rate of 28% (95% CI: 18-44) for a ΔTMTV ≥75%. The outcomes for ΔSUVmax &lt;65% and ΔTMTV &lt;75% at PET2 remained significant in a cox regression model adjusted for IPI and bulky disease (&gt;10cm)(Table). Conclusions: A ΔTMTV decline &lt;75% or a ΔSUVmax decline &lt;65% at PET2 identified an ultra-high-risk subgroup of DLBCL with particularly poor outcomes, that captured a high percentage of prDLBCL patients, and was significant after adjusting for IPI and bulky baseline disease. These patients may benefit from clinical trials evaluating alternative PET-adapted treatment strategies, but further evaluation among all patients with DLBCL is needed. [Table: see text]
Revisiting the optimal neoadjuvant immunotherapy regimen in resectable stage III melanoma based on the interferon gamma signature: A pooled analysis.
Authors: Minke W. Lucas, Petros Dimitriadis, Irene L.M. Reijers, Alexander M. Menzies, Elisa A. Rozeman, Judith M. Versluis, Alexander Chan Chi Huang, Sten Cornelissen, Annegien Broeks, Richard A. Scolyer, Tara C. Mitchell, Georgina V. Long, Christian U. Blank
Journal: Journal of Clinical Oncology (2023)

9516 Background: Neoadjuvant anti-PD1 has been shown to be superior to adjuvant administration. Combination of neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) induces even higher pathologic response rates (pRR) and event-free survival (EFS), but at the cost of higher toxicity. We previously showed that the interferon gamma (IFN-γ) signature is associated with a higher pRR after neoadjuvant IPI+NIVO. We hypothesized that IFN-γ high patients (pts) might benefit from less toxic anti-PD1 monotherapy (mono), while IFN-γ low pts might need an escalated regimen with IPI 3mg/kg + NIVO 1mg/kg. Methods: In this pooled analysis, pts with macroscopic nodal melanoma who received neoadjuvant NIVO 1mg/kg + IPI 3mg/kg (IPI3/NIVO1), IPI 1mg/kg + NIVO 3mg/kg (IPI1/NIVO3), sequential IPI 3mg/kg and NIVO 3mg/kg (IPI3&gt;NIVO3), or NIVO mono (240mg; IFN-γ high pts only) from the OpACIN-neo, PRADO and DONIMI trials, were analyzed according to their baseline IFN-γ signature. RNA gene expression from baseline tumor biopsies was analyzed using the Nanostring nCounter platform. The IFN-γ scores were calculated using an algorithm and cut-off previously developed at the NKI and prospectively tested in the DONIMI trial. Results: Baseline tumor material was available from 151 pts (Table). Median follow-up was 42 months for the entire cohort and 19 months for NIVO mono pts. Combined IPI+NIVO in IFN-γ high pts induced similar major pathologic response (MPR) rates compared to NIVO mono in IFN-γ high pts (71% vs 80%, p=0.715), and significantly higher MPR rates compared to IPI+NIVO in IFN-γ low pts (71% vs 45%, p=0.003). At 18-months, EFS rates were 87%, 100% and 73% respectively, and overall survival (OS) rates were 98%, 100% and 96%. Notably, IPI3/NIVO1 seemed to induce a higher MPR rate than IPI1/NIVO3 in IFN-γ low pts (64% vs 41%), which was not statistically significant due to small subgroups. At 36 months, EFS was 91% vs 62% and OS was 91% vs 82%. Conclusions: Neoadjuvant NIVO mono seems to have equal outcomes as IPI+NIVO in IFN-γ high pts. IFN-γ low pts may benefit from IPI+NIVO with higher doses of IPI. Incorporating baseline biomarkers like the IFN-γ signature algorithm in neoadjuvant treatment decisions will optimize the risk-benefit ratio for these pts. [Table: see text]
The impact of Covid-19 pandemic on breast cancer multidisciplinary management at the Vall d'Hebron University Hospital.
Authors: Isabel Pimentel, Cristina Viaplana, Carolina Ortiz, Guillermo Villacampa, Juan Aguilar-Company, Ana Rodriguez, Victoria Magdalena Reyes, Judith Balmana Gelpi, Xavier Martinez, Patricia Gómez Pardo, Miriam Arumí, Cristina Saura, Martin Espinosa-Bravo
Journal: Journal of Clinical Oncology (2023)

e18782 Background: The impact of breast cancer screening program interruption, restrictions and delays on diagnostic exams and access to primary care due to COVID-19 is not fully understood. We report our experience on breast cancer (BC) multidisciplinary management during 2020 in a Spanish COVID-19 reference centre, and the largest hospital in Catalonia. Methods: Cohort analysis of 2020 newly BC diagnosis, as compared to 2019 and 2018 period. Results: Overall, 54% less women were called to participate on the breast screening program and only 54% of those have accepted to take part of the program during March to May 2020 (lockdown period), as compared to 76% of acceptance in 2018/2019. Consequently, during the lockdown period there was a 38% reduction on breast oncologic surgeries and a 49% decrease on first medical oncology visits vs the same period of 2018/2019. Nevertheless, time from diagnosis to first oncologic treatment was similar between study periods. Stage IV BC diagnosis has doubled in 2020 representing 9.8% vs 4.2% and 4.8% in 2018 and 2019 respectively (p &lt; 0.001). Medical oncologists’ decision on dose dense (dd) or weekly paclitaxel chemotherapy exposure have not changed in 2020 vs 2019. Conclusions: COVID-19 pandemic has had a strong impact on screening programs, with the double of patients being diagnosed at advanced stage in 2020, as compared to the two previous years.
Multi-genomic analysis of compound and uncommon EGFR mutations in patients with non-small cell lung cancer.
Authors: Jayoung Park, Yu Min Lee, Sojeong Ka, Seoree Kim, In-Ho Kim, Yeoun Eun Sung, Chan-Kwon Jung, Jung-Young Shin, Sang Hoon Chun, Young Ho Lee, Jin Hyoung Kang, Joori Kim
Journal: Journal of Clinical Oncology (2023)

8534 Background: There are similar and different properties between the epidermal growth factor receptor mutations (mEGFR), which are classified into common, uncommon, and compound mutation subtypes depending on their location and pattern on the EGFR gene. We investigated the RWD and RNA expression profile of uncommon and compound mutations in the mEGFR+ NSCLC patients. Methods: We collected the medical information for stage I-IIIA mEGFR+ NSCLC patients receiving curative surgical resection in Seoul St. Mary’s Hospital. We explored the RNA expression profile using multiplex IF and High-Plex Digital Spatial Profiling. A total of 18,676 DEG libraries were constructed, and 151 significance genes with &gt; 2-fold changes, 4-log 2 normalized read counts, and p-value = 0.05 (up and down) were identified. Results: In hospital cohort, 941 mEGFR+ cases of total 6,609 cases consist of common, 860 (91.4%), uncommon, 60 (7.4%), and compound, 21 (2.2%). Median relapse-free survival in uncommon and compound mEGFRs (31.4M and 33.7M) was shorter than common mEGFRs (40.1M, p = 0.877), but median overall survival did not differ between the groups. CNS recurrence rates in the uncommon and compound mEGFRs (40.0% and 35.3%) tended to be higher than that of common mEGFRs (27.4%, p = 0.361). Spatial RNA-seq data of the ratio of deconvolution individual cells showed that genes involved in inflammatory and immune response were relatively lower in mEGFR+ groups. According to the difference in DEG library through clustering heat map, uncommon or compound mEGFR in the immune, inflammatory response category, extracellular matrix, RNA splicing gene category, JAK-STAT, p53, PI3K-AKT, and notch signaling pathway related genes were down regulated compared to common mEGFR+ group. Gene ontology string analysis revealed RNA expression of genes in compound mEGFR was functionally associated with chemokine production (23.4%), electron transfer activity (14.9%) and T cell selection (8.5%), and, in uncommon mEGFRs, was associated with regulation of oligopeptide transport (26.1%), hypermethylation of CpG island (21.7%), and CD4+ CD25+ αβ regulatory T cell lineage commitment (13.0%), compared to common mEGFR+ groups. Based on the GSEA, relatively highly clustered genes in compound mEGFR were the protein modification process, G-protein coupled receptor, regulation of cytosolic calcium ion concentration, and IL-5 production pathways, and lower ES levels in oxidative phosphorylation and RNA processing pathways, when compared to common mEGFR+ groups. Conclusions: In conclusion, our results suggest that uncommon and compound mEGFR+ subtypes exhibiting distinguished RNA expression profile of functional signaling pathways and protein network be not same disease entity as common mEGFR+ subtype.
Systematic review determining the characteristics of primary bone lymphoma.
Authors: Raed Benkhadra, Michael Auster, Tarek Nayfeh, Alzhraa S. Abbas, Reem Alsibai, Khalid Benkhadra, Paromita Datta, Supreet Kaur
Journal: Journal of Clinical Oncology (2023)

e19543 Background: Primary Bone Lymphoma (PBL) is defined as a lymphoma originating in an osseous site with no systemic disease. It is rare, constituting around 1% of all lymphomas. Due to its rarity, ascertaining natural history and standard of care treatments are based primarily on small case series but there have been no systematic reviews, randomized control trials or meta-analysis to establish optimal treatment strategies. Methods: We searched MEDLINE, Embase, Scopus and other sources, from each database's inception to September 2022. Outcomes of interest included mortality and progression at different time points, as well as complete response and partial response. Meta-analysis was conducted using the random-effects model. Results: The number of studies matching our inquiry was 51 ranging from 1955 to 2019. Total patients studied were 5,847 of which 3,055 were male and the dominant histology was diffuse large B cell lymphoma with 3,816. Treatment primarily consisted of radiation therapy, chemotherapy, or a combination of the two. Overall mortality at 2, 5 and 10 years was 17%, 29% and 39% respectively. Complete response to initial treatment was noted in 73% of patients. Disease progression at 2 and 5 years was 26% and 29% respectively. Patients aged older than 60 years and multiple sites of disease in the skeleton (such as axial and spine etc.) had worse outcomes with RR 1.76 (P value 0.0027) and 1.133 (P value 0.0167) respectively. Additionally, patients who underwent chemotherapy with radiation vs radiation alone had improved outcomes with a relative risk of 0.38 (P value of 0.0001). Patients who underwent radiation treatment in addition to chemotherapy tended to have improved outcomes with a relative risk of 0.60 but this was not statistically significant with a P value of 0.068. Conclusions: We performed a systematic review to determine the characteristics and current treatment of PBL. The analysis demonstrates the rarity and heterogenicity of the disease. The current standard of care is for chemoradiation, but this is based primarily on old case studies. Our study confirms the utility of multimodal treatment with a tendency for improved outcomes. However, further prospective trials are needed to determine the necessity of multimodal treatment given this hypothesis generating study. [Table: see text]
Immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma: Real-world evidence.
Authors: Erica C. Koch Hein, Maysa Vilbert, Ian Hirsch, Mauricio Fernando Ribeiro, Luke Mantle, Cynthia Fournier, Marcus O. Butler, Anna Spreafico, Samuel Saibil
Journal: Journal of Clinical Oncology (2023)

e21519 Background: Immune checkpoint inhibitors (ICI) Cemiplimab and Pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate efficacy and safety of ICI in a real-world cSCC population, including patients with conditions which would exclude trial participation. Methods: In this single-center retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We aimed to assess efficacy outcomes according to age, comorbidities, and immune-related adverse events (irAE). Best overall response (BOR) was investigator-assessed. X 2 , Fisher’s exact, and Mann-Whitney U tests were used to compare subgroups of interest, and Cox proportional hazards models were fitted. The log-rank test was used to assess progression free survival (PFS) and overall survival (OS). Results: We identified 35 patients. Characteristics are displayed in the table. Median follow-up was 21.8 months (95% CI 19.3-24.4). BOR to ICI was partial response (PR) in 42.9%, complete response (CR) in 28.6%, and stable disease in (SD) 14.3% of patients. Main reasons for discontinuation of treatment were progression of disease (PD) in 20%, achievement of maximum benefit in 17.1%, and toxicities in 14.3%. Treatment beyond progression was given to 22.9% patients. The PFS rate at 1 year was 62%; median PFS was not reached (NR). PFS and OS were similar between patients with or without comorbidities, ECOG performance status 0-1 versus 2-3, or between age groups ≥75 years versus &lt;75. IrAE grade 1-2 and 3-4 were seen in 80% and 14.3% of patients, respectively. Patients with grade 1-2 irAE had greater PFS than those without toxicities (HR 0.16; 95%CI 0.045-0.567, p=0.005). The OS rate at 1 year was 76%, with a median OS of 38.57 months (95% CI 19.4-57.7). Responders (CR+PR) had a prolonged median OS compared to non-responders (SD+PD): 38.57 months versus 9 months (HR 0.083; 95%CI 0.17-0.406, p=0.002). Conclusions: ICI were effective and safe among real-world cSCC patients, independent of age, comorbidities or ECOG. Our BOR was higher than in the published clinical trials, which might reflect the subjective nature of investigator-assessed response or the small sample size assessed. [Table: see text]
Italian report of expanded access for nab-sirolimus in patients with malignant perivascular epithelioid cell tumor (PEComa).
Authors: Roberta Sanfilippo, Chiara Fabbroni, Elena Fumagalli, Andrea Franza, Salvatore Provenzano, Paola Collini, Francesca Gabriella Greco, Matteo Duca, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2023)

e23541 Background: Malignant perivascular epithelioid cell tumor (PEComa) is a rare aggressive sarcoma, with no approved treatment in Europe, while the mechanistic target of rapamycin (mTOR) inhibitor nab-sirolimus has been approved in US. In Europe, an expanded access program is available for patients with advanced or metastatic PEComa. Methods: We retrospectively collected data of patients with advanced/metastatic PEComa treated at our institution from December 2020 through 3 rd February 2023 with nab-sirolimus. Nab-sirolimus was administered as an intravenous infusion over 30 minutes at a dosage of 100 mg/m2 on days 1 and 8 of each 21-day cycle. Results: At the time of this analysis, 10 patients were treated with nab-sirolimus and 8 are evaluable for response. Of them, 4 patients received nab-sirolimus as their first mTOR inhibitor therapy, while 4 had already received another mTOR inhibitor, being discontinued for PD. Amongst patients not pretreated with mTOR inhibitors, 2/4 had a PR as their best response, 1/4 obtained SD and 1/4 obtained PD. Amongst patients pretreated with another mTOR inhibitor, all but 1 obtained PD as their best response and 1/4 had SD. The majority of nab-sirolimus-related adverse events were grade 1 or 2 and were manageable for long-term treatment. No grade 4 treatment-related adverse events were observed. Amongst the 10 patients treated with nab-sirolimus, tumor profiling is available for 6 patients, being ongoing for the other 4. Conclusions: nab-Sirolimus is active in patients with malignant PEComa. Activity is mainly confined to those not already treated with other mTOR inhibitors.
Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: An open-label phase II study.
Authors: Nian Lu, Yao-fei Jiang, Weixiong Xia, Ying Huang, Chuan-miao Xie, Cheng Xu, Yan-Fang Ye, Guo-Ying Liu, Wei-Xin Bei, Liang-Ru Ke, Wang-Zhong Li, Xin Wang, Changqing Xie, Hu Liang, Xiang Yanqun
Journal: Journal of Clinical Oncology (2023)

6031 Background: There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in mNPC patients where platinum-based chemotherapy has failed. Methods: This was a single-center, open-label, single-arm, phase II trial for mNPC patients progressed after at least one line of systemic therapy. Patients were enrolled and received sintilimab (200 mg) plus bevacizumab (7.5mg/kg) intravenously every 3 weeks. The primary end point was objective response rate (ORR) assessed by investigators following the guidelines of RECIST 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This trial is registered with ClinicalTrials.gov (NCT04872582). Results: Thirty-three patients were enrolled. Median age was 46 years (range, 18-64 years), and 63.6% of patients had previously received two or more lines of chemotherapy for metastatic disease. Median follow-up was 7.6 months (range, 4.1-17.5 months). ORR was 54.5% (95% CI, 36.4- 71.9%) with 3 complete responses (9.1%) and 15 partial responses (45.5%). Median PFS was 6.8 months (95% CI, 5.2 months to not estimable). Median DOR was 7.2 months (95% CI, 4.4 months to not estimable). Median OS was not reached. The most common potential immune-related AE was grade 1-2 hypothyroidism (42.4%). Treatment-related grade 3 or 4 adverse events (AEs) occurred in 7 patients (21.2%), including nasal necrosis (9%), hypertension (3%), pruritus (3%), total bilirubin increased (3%) and anaphylactic shock (3%). No treatment-related deaths and severe epistaxis occurred. Conclusions: This phase II trial showed that sintilimab plus bevacizumab demonstrated promising antitumor activity and manageable toxicities in mNPC patients after failure of platinum-based chemotherapy. Clinical trial information: NCT04872582 .
DelPHI: A novel program to accelerate access to precision oncology in the community oncology setting.
Authors: Anthony Martin Magliocco, Roy Khalife, Catherine Wilson, Tara M Love, Rama Balaraman
Journal: Journal of Clinical Oncology (2023)

e18713 Background: It has been well recognized that the rapid advances in precision oncology have not fully been translated into improved access for community cancer programs in the USA, where as much as 95% of oncological assessment and treatment occurs. To address this growing gap, Protean BioDiagnostics and Roche Information Solutions have created a novel project to improve the Delivery of Precision Health Information (DelPHI) to community-based oncology programs using an innovative precision oncology testing system (MAPS™) integrated with a digital decision support and telemedicine framework (navify). The project seeks to bridge the clinical and administrative gaps to help bring precision oncology to the community. Methods: In an initial implementation of DelPHI, 28 cases were analyzed from a community oncology clinic. Analyses included immunohistochemistry (IHC) testing, rapid molecular testing, and a 523-gene DNA, 55-gene RNA comprehensive cancer panel. These cases were grouped together and queried for IA actionability alterations, potentially actionable alterations, potentially germline, pathogenic variants, time to each step, diagnosis changes, and noted if there were any inadequate case materials. Results: Based on the 28 patients that were run (13 lung, 4 breast, 1 prostate, 2 colorectal, 2 gastric, 1 esophagus, 1 melanoma, 2 bladder, 1 glioma, 1 poorly differentiated carcinoma), 50 total actionable alterations were detected. 90% of the patients had at least one potentially actionable alteration, 46% of patients had a IA actionability alteration, and 29% of patients had a potentially pathogenic germline variant that may warrant further testing. We identified 2/28 patients with incorrect diagnoses that were corrected after testing. 23/28 patients underwent testing via the large, comprehensive panel, and 16 of these 23 had additional targets. 3 individuals had inadequate tissue to analyze, and 1 patient had an ALK expression imbalance that was not seen in other tests, which may be due to heterogeneity of the sample; both of these issues may benefit from liquid biopsies. Conclusions: Precision medicine can be delivered to community cancer centers using a combined integrated molecular testing system coupled with a digital knowledge support framework leading to improved speed of patient testing and uncovering of actionable biomarkers. Numerous challenges were identified, including delays in accessing tissue and limited tissue availability. These challenges could be overcome with alternative testing approaches, such as liquid biopsy and education to improve strategies for tissue collection and management.